Sexual dysfunction and self-perceived sexual health in patients with rheumatoid arthritis and systemic lupus erythematosus: results from a cross-sectional survey.

Sexual dysfunction (SD) has been associated with worse quality of life and higher disease activity in patients with rheumatic diseases, yet it is still not regularly addressed during routine rheumatologic evaluations. This study aimed to determine the prevalence of sexual dysfunction in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and evaluate their perception of their sexual health. We performed a retrospective study in an outpatient rheumatology clinic to evaluate patients over 18 years old with a diagnosis of RA or SLE through the Spanish version of the Arizona Sexual Experiences Scale (ASEX) and the Sexual Health Perception Survey (SHEPS), a questionnaire of 6 items designed in our clinic. Additionally, we applied the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F version 4) and the Hospital Anxiety and Depression Scale (HADS). A total of 567 patients were evaluated with SHEPS, most of whom were women with a median age of 50 years (IQR: 34) and a median disease duration of 5 years (IQR: 9). Through the ASEX, we found that 67% of the patients with RA and 60% of the patients with SLE experienced SD. Patients reported the level of sex drive, arousal, and the ability to achieve orgasms as the areas with the most difficulties. Most patients did not know their disease could affect their sexuality and had never addressed these issues with their rheumatologists, but almost all of them were willing to. Our findings highlight the importance of addressing sexual health issues regularly during rheumatologic evaluations.

Scalable weaving of resilient membranes with on-demand superwettability for high-performance nanoemulsion separations.

This study leverages the ancient craft of weaving to prepare membranes that can effectively treat oil/water mixtures, specifically challenging nanoemulsions. Drawing inspiration from the core-shell architecture of spider silk, we have engineered fibers, the fundamental building blocks for weaving membranes, that feature a mechanically robust core for tight weaving, coupled with a CO2-responsive shell that allows for on-demand wettability adjustments. Tightly weaving these fibers produces membranes with ideal pores, achieving over 99.6% separation efficiency for nanoemulsions with droplets as small as 20 nm. They offer high flux rates, on-demand self-cleaning, and can switch between sieving oil and water nanodroplets through simple CO2/N2 stimulation. Moreover, weaving can produce sufficiently large membranes (4800 cm2) to assemble a module that exhibits long-term stability and performance, surpassing state-of-the-art technologies for nanoemulsion separations, thus making industrial application a practical reality.

Nanoplasmonic Single-Tumoroid Microarray for Real-Time Secretion Analysis.

Organoid tumor models have emerged as a powerful tool in the fields of biology and medicine as such 3D structures grown from tumor cells recapitulate better tumor characteristics, making these tumoroids unique for personalized cancer research. Assessment of their functional behavior, particularly protein secretion, is of significant importance to provide comprehensive insights. Here, a label-free spectroscopic imaging platform is presented with advanced integrated optofluidic nanoplasmonic biosensor that enables real-time secretion analysis from single tumoroids. A novel two-layer microwell design isolates tumoroids, preventing signal interference, and the microarray configuration allows concurrent analysis of multiple tumoroids. The dual imaging capability combining time-lapse plasmonic spectroscopy and bright-field microscopy facilitates simultaneous observation of secretion dynamics, motility, and morphology. The integrated biosensor is demonstrated with colorectal tumoroids derived from both cell lines and patient samples to investigate their vascular endothelial growth factor A (VEGF-A) secretion, growth, and movement under various conditions, including normoxia, hypoxia, and drug treatment. This platform, by offering a label-free approach with nanophotonics to monitor tumoroids, can pave the way for new applications in fundamental biological studies, drug screening, and the development of therapies.

Mitral Annular Disease at Cardiac MRI: What to Know and Look For.

Accurate evaluation of the mitral valve (MV) apparatus is essential for understanding the mechanisms of MV disease across various clinical scenarios. The mitral annulus (MA) is a complex and crucial structure that supports MV function; however, conventional imaging techniques have limitations in fully capturing the entirety of the MA. Moreover, recognizing annular changes might aid in identifying patients who may benefit from advanced cardiac imaging and interventions. Multimodality cardiovascular imaging plays a major role in the diagnosis, prognosis, and management of MV disease. Transthoracic echocardiography is the first-line modality for evaluation of the MA, but it has limitations. Cardiac MRI (CMR) has emerged as a robust imaging modality for assessing annular changes, with distinct advantages over other imaging techniques, including accurate flow and volumetric quantification and assessment of variations in the measurements and shape of the MA during the cardiac cycle. Mitral annular disjunction (MAD) is defined as atrial displacement of the hinge point of the MV annulus away from the ventricular myocardium, a condition that is now more frequently diagnosed and studied owing to recent technical advances in cardiac imaging. However, several unresolved issues regarding MAD, such as the functional significance of pathologic disjunction and how this disjunction advances in the clinical course, require further investigation. The authors review the role of CMR in the assessment of MA disease, with a focus on MAD and its functional implications in MV prolapse and mitral regurgitation. ©RSNA, 2024 Supplemental material is available for this article. See the invited commentary by Stojanovska and Fujikura in this issue.

Mentha spp. essential oils: toxicity to Alphitobius diaperinus, activity against poultry pathogenic bacteria, and Beauveria bassiana compatibility.

The botanical insecticide market is growing because of limitations placed on the use of certain synthetic chemical insecticides. In this sense, the lesser mealworm Alphitobius diaperius (Coleoptera: Tenebrionidae) is the main poultry pest. The insect causes weight loss and damage to the digestive system of poultry, and it is a vector and reservoir of pathogens. Consequently, this study explored the following hypotheses: (i) essential oils (EOs) derived from Mentha spp. are toxic to A. diaperius; (ii) these EOs are compatible with Beauveria bassiana, the natural enemy of the poultry pest, that parasite A. diaperinus; (iii) these EOs also exhibit activity against bacteria that are pathogenic to poultry. In topical applications and ingestion tests, EOs from Mentha arvensis, Mentha spicata, and Mentha piperita were toxic to A. diaperinus. Chromatographic analyses revealed that menthol is the predominant compound in M. arvensis and M. piperita, whereas carvone is the major compound in M. spicata. Both (-)- and (+)-menthol, along with (-)- and (+)-carvone, underwent testing with A. diaperinus. Nevertheless, their activity was not as potent as those of the EOs, suggesting a possible synergistic and/or additive effect. The EOs did not have any adverse effects on the conidial germination, vegetative growth, or conidia production per colony of the entomopathogenic fungus B. bassiana. Consequently, these EOs are compatible with this natural enemy. The EO extracted from M. spicata exhibited significant toxicity against Staphylococcus aureus (ATCC 25923), whereas the remaining EOs displayed moderate toxicity against this bacterium. The EOs derived from Mentha spp., as assessed in this study, hold promise for the development of botanical insecticides tailored for the control of A. diaperinus. These insecticides are selective in favor of the natural enemy B. bassiana and can also serve as effective sanitizers, thanks to their antibacterial properties.

RNA Expression of MMP12 Is Strongly Associated with Inflammatory Bowel Disease and Is Regulated by Metabolic Pathways in RAW 264.7 Macrophages.

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including inflammatory bowel disease. Although previously published data suggested that the modulation of MMP12 in macrophages could be a determinant for the development of intestinal inflammation, scarce information is available on the mechanisms underlying the regulation of MMP12 expression in those phagocytes. Therefore, in this study, we aimed to delineate the association of MMP12 with inflammatory bowel disease and the molecular events leading to the transcriptional control of this metalloproteinase. For that, we used publicly available transcriptional data. Also, we worked with the RAW 264.7 macrophage cell line for functional experiments. Our results showed a strong association of MMP12 expression with the severity of inflammatory bowel disease and the response to relevant biological therapies. In vitro assays revealed that the inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and the stimulation of the AMP-activated protein kinase (AMPK) signaling pathway potentiated the expression of Mmp12. Additionally, AMPK and mTOR required a functional downstream glycolytic pathway to fully engage with Mmp12 expression. Finally, the pharmacological inhibition of MMP12 abolished the expression of the proinflammatory cytokine Interleukin-6 (Il6) in macrophages. Overall, our findings provide a better understanding of the mechanistic regulation of MMP12 in macrophages and its relationship with inflammation.

Tuning Pore Size in Graphene in the Angstrom Regime for Highly Selective Ion-Ion Separation.

Zero-dimensional pores spanning only a few angstroms in size in two-dimensional materials such as graphene are some of the most promising systems for designing ion-ion selective membranes. However, the key challenge in the field is that so far a crack-free macroscopic graphene membrane for ion-ion separation has not been realized. Further, methods to tune the pores in the Å-regime to achieve a large ion-ion selectivity from the graphene pore have not been realized. Herein, we report an Å-scale pore size tuning tool for single layer graphene, which incorporates a high density of ion-ion selective pores between 3.5 and 8.5 Å while minimizing the nonselective pores above 10 Å. These pores impose a strong confinement for ions, which results in extremely high selectivity from centimeter-scale porous graphene between monovalent and bivalent ions and near complete blockage of ions with the hydration diameter, DH, greater than 9.0 Å. The ion diffusion study reveals the presence of an energy barrier corresponding to partial dehydration of ions with the barrier increasing with DH. We observe a reversal of K+/Li+ selectivity at elevated temperature and attribute this to the relative size of the dehydrated ions. These results underscore the promise of porous two-dimensional materials for solute-solute separation when Å-scale pores can be incorporated in a precise manner.

Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti-Inflammatory Effects.

In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034 µM in A-431, 2.67 µM in MCF-7, and 3.64 µM in AGS) without showing activity on the non-tumorigenic cell line (>100 µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.

The agavins (Agave carbohydrates) story.

Fructans, are carbohydrates defined as fructose-based polymers with countable degree of polymerization (DP) ranging so far from DP3 to DP60. There are different types of fructans depending on their molecular arrangement. They are categorized as linear inulins and levans, neoseries of inulin and levan, branched graminans, and highly branched neofructans, so called agavins (Agave carbohydrates). It is worth to note that agavins are the most recently described type of fructans and they are also the most complex ones. The complexity of these carbohydrates is correlated to their various isomers and degree of polymerization range, which is correlated to their multifunctional application in industry and human health. Here, we narrate the story of the agavins' discovery. This included their chemical characterization, their benefits, biotechnological applications, and drawbacks over human health. Finally, a perspective of the study of agavins and their interactions with other metabolites through metabolomics is proposed.

Right Ventricle and Autoimmune Diseases.

Autoimmune diseases can express pathologies in specific organs (e.g. thyroid, pancreas, skin) or generate systemic pathologies (generalized lupus erythematosus, rheumatoid arthritis, systemic sclerosis), the latter usually present systemic inflammatory phenomena. Some studies have reported alterations in right ventricular contractility in patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and juvenile idiopathic arthritis, which may contribute to the known outcome of increased cardiovascular risk. However, there is not much information available on the causes that generate these alterations, the most likely being small vessel damage and fibrosis due to subclinical inflammation.1-5 In this sense, the disease in which the alterations of the right ventricle have been more studied is systemic sclerosis, specifically at the changes induced due to pulmonary arterial hypertension, this being one of the main causes of death in this group of patients after the significant decrease in mortality associated with the sclerodermic renal crisis with the treatment of angiotensin-converting enzyme inhibitors. In this review, we will focus on explaining the structural and functional changes that occur in the right ventricle of patients with systemic sclerosis, from early alterations to late complications. In this context, it is necessary to distinguish between right heart alterations that occur in patients with systemic sclerosis and pulmonary arterial hypertension and those that occur without pulmonary arterial hypertension and that can be attributed to other causes such as microvascular damage or myocardial fibrosis.

Evolution of cooperation in a two-species system with a common resource pool.

Understanding the evolution of cooperation is a major question in Evolutionary Biology. Here, we extend a previously proposed mathematical model in Evolutionary Game Theory that investigated how resource use by a single species composed of cooperators and defectors may lead to its maintenance or extinction. We include another species in the model, so as to investigate how different intra and interspecific interactions of cooperative or competitive nature among individuals that share the same essential resource may drive the survival and evolution of the species. Several outcomes emerge from the model, depending on the configuration of the payoff matrix, the individual contribution to the resource pool, the competition intensity between species, and the initial conditions of the system dynamics. Observed results include scenarios in which species thrive due to the action of cooperators, but also scenarios in which both species collapse due to lack of cooperation and, consequently, of resources. In particular, a high initial availability of resources may be the determinant factor to the survival of both species. Interestingly, cooperation may be more favored when individuals have less incentive to cooperate with others, and the survival of their populations may depend crucially on their competitive capacities.

The Pseudomonas syringae pv. tomato DC3000 effector HopD1 interferes with cellular dynamics associated with the function of the plant immune protein AtNHR2B.

The plant pathogenic bacterium Pseudomonas syringae pv tomato DC3000 (Pst DC3000) causes disease in tomato, in the model plant Arabidopsis thaliana, and conditionally in Nicotiana benthamiana. The pathogenicity of Pst DC3000 is mostly due to bacterial virulence proteins, known as effectors, that are translocated into the plant cytoplasm through the type III secretion system (T3SS). Bacterial type III secreted effectors (T3SEs) target plants physiological processes and suppress defense responses to enable and support bacterial proliferation. The Pst DC3000 T3SE HopD1 interferes with plant defense responses by targeting the transcription factor NTL9. This work shows that HopD1 also targets the immune protein AtNHR2B (Arabidopsis thaliana nonhost resistance 2B), a protein that localizes to dynamic vesicles of the plant endomembrane system. Live-cell imaging of Nicotiana benthamiana plants transiently co-expressing HopD1 fused to the epitope haemagglutinin (HopD1-HA) with AtNHR2B fused to the red fluorescent protein (AtNHR2B-RFP), revealed that HopD1-HA interferes with the abundance and cellular dynamics of AtNHR2B-RFP-containing vesicles. The results from this study shed light into an additional function of HopD1 while contributing to understanding how T3SEs also target vesicle trafficking-mediated processes in plants.

Using High-Resolution Anoscopy to Detect Anal Dysplasia Due to Papillomavirus in Patients with Inflammatory Bowel Disease

Introduction: Anal squamous cell carcinoma is rare, but its incidence and mortality have been increasing globally; 90% of cases are related to human papillomavirus (HPV) infection(1,2). Patients with inflammatory bowel disease (IBD) have a higher risk of infection with this virus; an incidence of 5.5 per 100,000 patients has been identified in the IBD group compared to 1.8 in the non-IBD group(3). Materials and methods: A descriptive case series study was conducted with 21 patients with IBD and no perianal symptoms between January and July 2022 at the Institute of Coloproctology in Medellín. They underwent anal cytology, HPV genotyping, and high-resolution anoscopy after explanation and acceptance of the procedure. If lesions were found, ablative treatment was performed. Results: 23% of this cohort had low-grade squamous lesions, while 14.2% had high-grade lesions with dysplasia changes during anoscopy. Besides, 90.4% had positive HPV genotyping, of which 76.1% were high-grade. Conclusions: Our study suggests that this series of patients with IBD behaves as a high-risk group for developing premalignant lesions in association with HPV. High-resolution anoscopy is a cost-effective, painless, and affordable method that, in expert hands, may impact the diagnosis and management of premalignant lesions and decrease the incidence of anal cancer in patients with IBD.

Introducción: El carcinoma anal de células escamosas es raro, pero su incidencia y mortalidad han ido en aumento globalmente. El 90% de los casos están relacionados con la infección por el virus del papiloma humano (VPH)1,2 y los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de infección por este virus; se ha identificado una incidencia de 5,5 por 100.000 pacientes en el grupo de EII frente a 1,8 en el grupo sin EII3. Metodología: Se realizó un estudio descriptivo de serie de casos en el que se incluyó a 21 pacientes con EII, sin síntomas perianales, entre enero y julio de 2022 en el Instituto de Coloproctología de Medellín, a quienes se les realizó citología anal, genotipificación del VPH y anoscopia de alta resolución, previa explicación y aceptación del procedimiento. Si se encontraban lesiones, se realizaba tratamiento ablativo. Resultados: El 23% de esta cohorte tenía lesiones escamosas de bajo grado, mientras que el 14,2% presentaba lesiones de alto grado con cambios de displasia al momento de la anoscopia. El 90,4% tenían genotipificación positiva para VPH, de los cuales el 76,1% eran de alto grado. Conclusiones: Nuestro estudio sugiere que esta serie de pacientes con EII se comporta como un grupo de alto riesgo para desarrollar lesiones premalignas en asociación con el VPH. La anoscopia de alta resolución es un método rentable, indoloro y asequible que, en manos expertas, puede impactar el diagnóstico y manejo de lesiones premalignas y disminuir la incidencia de cáncer anal en pacientes con EII.

Acute quetiapine overdose is associated with risk of ectopic atrial rhythm.

Quetiapine overdose is commonly associated with coma, respiratory depression, hypotension, tachycardia, and QTc interval prolongation on the electrocardiogram.

Exceso de peso y antecedentes heredofamiliares, una oportunidad de acción desde la Universidad / Excess weight and hereditary family history, an opportunity for action from the University

Resumen Objetivo: Identificar a los estudiantes con sobrepeso y obesidad, con antecedentes heredofamiliares para hipertensión y diabetes mellitus y sus hábitos de salud. Materiales y métodos: Cuestionario en línea. Participaron estudiantes de primer ingreso de diferentes programas académicos. Se incluyeron aspectos de antecedentes heredofamiliares, índice de masa corporal, y hábitos de salud. Se estimó asociación por regresión logística. Resultados: De 1211 estudiantes el 68% fueron mujeres. Se reportó bajo peso 10%, normo peso 65% y exceso de peso 25%. El 28% tuvo antecedentes heredo familiares (AHF) para diabetes mellitus y 14% para hipertensión. En un análisis estratificado por sexo, el consumo de alcohol se asoció a exceso de peso en los hombres (OR = 2.3, IC95% [1.1-5.0], p = 0.031); y en las mujeres lo fue el AHF para hipertensión arterial (OR = 2.2, IC95% [1.3-3.7], p = 0.004). Conclusión: Ser hombre, fumar, consumo de alcohol y AHF para hipertensión arterial fueron factores asociados a exceso de peso. En las universidades todavía es tiempo para establecer un proyecto de acción para mantener y promocionar la salud.

Abstract Objective: Identify overweight and obese students with a family history of hypertension and diabetes mellitus and their health habits at the University Center of Health Sciences. Materials and methods: Online questionnaire. First year students of different academic programs participated. Aspects of hereditary family history, body mass index, and health habits were included. Association was estimated by logistic regression. Results: Out of 1755 students, 68% were women. Low weight 10%, normal weight 65% and excess weight 25% were reported. 28% had a hereditary family history (AHF) for diabetes mellitus and 14% for hypertension. In an analysis stratified by sex, alcohol consumption was associated with excess weight in men (OR = 2.3, IC95% [1.1-5.0], p = 0.031); and in women it was AHF for arterial hypertension (OR = 2.2, IC95% [1.3-3.7], p = 0.004). Conclusion: Being a man, smoking, alcohol consumption and AHF for arterial hypertension were factors associated with excess weight. At universities, is still time to an action project to maintain and promote health.

Agave amica a potential model for the study of agavins metabolism.

Fructans found in agave are called agavins, highly branched neo-fructans. They are essential on the yield and quality of Tequila production. The need for agave specimens with higher accumulation of agavins became essential before the growing demand of such products. To get such specimens, understanding agavins metabolism is a quintessential requirement. For this, a more efficient biological model is required. The recently reclassified Agave amica possesses the potential to gather the requirements for becoming such a model. Therefore, this study dealt with the characterization of carbohydrates in the bulbs of A. amica focusing on fructans. Moreover, it tested and described its feasibility as model for the accelerated study of agavins. Infrared analysis unveiled potential content of fructans in the bulbs of A. amica. Furthermore, high performance thin layer chromatography detected fructooligosaccharides. High performance anion exchange chromatography confirmed a polydisperse mixture of branched fructans. Gas chromatography-mass spectrometry analysis demonstrated agavins like structures in the bulbs of A. amica. Moreover, total fructan content and multivariate data analysis through bulb's age demonstrated their correlation. Thus, the presence of agavins, their correlation with phenology, and their technical advantages highlighted the feasibility of this species as a potential new biological model for the study of agavins' metabolism.

Animal Model Standardization for Studying Avascular Necrosis of the Femoral Head in Legg-Calvé-Perthes Disease.

Objective Testing an experimental model for ischemic necrosis of the femoral head in Legg-Calvé-Perthes disease by evaluating gait, imaging and morphohistology. Methods The operation was done in 11 piglets. Necrosis by cerclage in the right femoral neck was induced. Piglets were divided into group A, with 8 animals, euthanizing two in the 2 nd , 4 th , 6 th , and 8 th weeks, respectively; and group B, with 2 animals ( sham ), submitted to the surgical procedure without cerclage of the right femoral neck. The gait classification used was that of Etterlin. The frozen femurs were submitted to digital radiography and computed tomography. The height and width of the epiphysis and epiphysary coefficient were measured at study times. Light microscopy and immunohistochemistry with TGF-ß1 were performed. Results One animal died of sepsis in Group A. In this group, claudication was observed in all animals. On digital radiography and computed tomography, bone sclerosis, enlargement of the right femoral neck, flattening, collapse, and fragmentation of the right femoral head were observed. All epiphysis height and epiphysary coefficient values of the right femoral head were lower than the contralateral ones, in which were observed chondrocytes disordered and separated by gaps. A reduction in TGF-ß1 expression was observed at 2 and 6 weeks in the right femoral head and at eight in the left. In group B, there were no signs of necrosis and gait was normal. Conclusions The model presented reproduced macroscopic necrosis on digital radiography, computed tomography, and microscopy. Gait evaluation showed a good correlation with other ischemia findings. Level of Evidence V. Diagnostic studies.

Toxoplasma gondii infection of the central nervous system and suicide: A case-control study of decedents.

We sought to determine the association between Toxoplasma gondii (T. gondii) infection of the central nervous system and suicide in a sample of decedents in Mexico City. One hundred and forty-seven decedents (87 who committed suicide and 60 who did not commit suicide) were studied. Brain tissues (amygdala and prefrontal cortex) of decedents were examined for the detection of T. gondii using immunohistochemistry. Detection of T. gondii was positive in 7 (8.0%) of the 87 cases (6 found in prefrontal cortex and one in amygdala), and in one (1.7%) of the 60 controls (found in prefrontal cortex) (OR: 5.16; 95% CI: 0.61-43.10; P = 0.14). Results suggest that T. gondii infection in brain is not associated with suicide. Further studies to confirm this finding are needed.